An investigation of phenylthiazole antiflaviviral agents

Bioorg Med Chem. 2011 Jun 15;19(12):3845-54. doi: 10.1016/j.bmc.2011.04.041. Epub 2011 May 3.


Flaviviruses are one of the most clinically important pathogens and their infection rates are increasing steadily. The phenylthiazole ring system has provided a template for the design and synthesis of antiviral agents that inhibit the flaviviruses by targeting their E-protein. Unfortunately, there is a correlation between phenylthiazole antiflaviviral activity and the presence of the reactive and therefore potentially toxic mono- or dibromomethyl moieties at thiazole-C4. Adding a linear hydrophobic tail para to the phenyl ring led to a new class of phenylthiazole antiflaviviral compounds that lack the toxic dibromomethyl moiety. This led to development of a drug-like phenylthiazole 12 that had high antiflaviviral selectivity (TI=147).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Flavivirus / drug effects*
  • Humans
  • Models, Molecular
  • Rats
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*


  • Antiviral Agents
  • Thiazoles